Background: Augmentation of insulin secretory response (ISR) in pregnancy has been attributed to a pregnancy-associated reduction in insulin sensitivity. We hypothesized that ISR in pregnancy increases prior to and independent of decrements in insulin sensitivity.
Methods: In 34 women, ISR (by intravenous glucose tolerance test) and insulin sensitivity (by euglycemic clamp) were assessed prior to pregnancy, in early pregnancy (12-14 weeks gestation), and in late pregnancy (34-36 weeks gestation). In a secondary analysis of data from a prior study, we used mixed effects models to compare ISR and insulin sensitivity in early pregnancy to the same parameters prior to pregnancy and in late pregnancy, with adjustment for age, obesity, and GDM status. We next explored the relationship between ISR and circulating hormones.
Results: ISR increased from prior to pregnancy to early pregnancy (unadjusted mean [standard deviation] 1st phase insulin response 465.1 [268.5] to 720 [358.2], P<0.001) and from early pregnancy to late pregnancy (to 924 [494.6], P=0.01). Insulin sensitivity increased from prior to pregnancy to early pregnancy (insulin sensitivity index 0.10 [0.04] to 0.12 [0.05], P=0.001) and decreased in late pregnancy (to 0.06 [0.03], P<0.001). Adjustment for insulin sensitivity did not attenuate observed augmentation in ISR in early pregnancy (P <0.001), but did eliminate the augmentation of ISR between early pregnancy and late pregnancy (P=0.30). Adjustment for age, obesity, and GDM status did not affect longitudinal changes in physiologic parameters. Leptin was positively associated with ISR, independent of insulin sensitivity and adiposity (P=0.004). Adjustment for leptin attenuated the augmentation of ISR in early pregnancy (adjusted mean change 121.5, P=0.13).
Conclusion: ISR increases markedly in early pregnancy, prior to and independent of the late pregnancy decrement in insulin sensitivity. Circulating hormones may mediate this metabolic adaptation.
C.E. Powe: None. L. Presley: None. J.J. Locascio: None. P. Catalano: None.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD22965); National Center for Research Resources (UL1RR024989); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK113218); Robert Wood Johnson Foundation; National Center for Advancing Translational Sciences (UL1TR002541)